Control of Initiation, Rate, and Routing of Spontaneous Capillary-Driven Flow of Liquid Droplets through Microfluidic Channels on SlipChip

This Article describes the use of capillary pressure to initiate and control the rate of spontaneous liquid–liquid flow through microfluidic channels. In contrast to flow driven by external pressure, flow driven by capillary pressure is dominated by interfacial phenomena and is exquisitely sensitive to the chemical composition and geometry of the fluids and channels. A stepwise change in capillary force was initiated on a hydrophobic SlipChip by slipping a shallow channel containing an aqueous droplet into contact with a slightly deeper channel filled with immiscible oil. This action induced spontaneous flow of the droplet into the deeper channel. A model predicting the rate of spontaneous flow was developed on the basis of the balance of net capillary force with viscous flow resistance, using as inputs the liquid–liquid surface tension, the advancing and receding contact angles at the three-phase aqueous–oil–surface contact line, and the geometry of the devices. The impact of contact angle hysteresis, the presence or absence of a lubricating oil layer, and adsorption of surface-active compounds at liquid–liquid or liquid–solid interfaces were quantified. Two regimes of flow spanning a 104-fold range of flow rates were obtained and modeled quantitatively, with faster (mm/s) flow obtained when oil could escape through connected channels as it was displaced by flowing aqueous solution, and slower (micrometer/s) flow obtained when oil escape was mostly restricted to a micrometer-scale gap between the plates of the SlipChip (“dead-end flow”). Rupture of the lubricating oil layer (reminiscent of a Cassie–Wenzel transition) was proposed as a cause of discrepancy between the model and the experiment. Both dilute salt solutions and complex biological solutions such as human blood plasma could be flowed using this approach. We anticipate that flow driven by capillary pressure will be useful for the design and operation of flow in microfluidic applications that do not require external power, valves, or pumps, including on SlipChip and other droplet- or plug-based microfluidic devices. In addition, this approach may be used as a sensitive method of evaluating interfacial tension, contact angles, and wetting phenomena on chip

Crown Ether-Metal ‘Sandwiches’ As Linking Mechanisms in Assembled Nanoparticle Films

Crown ether ligands attached to monolayer-protected clusters (MPCs) were assembled as films and the linking mechanism between the crown ether–metal ion–crown ether bridges between nanoparticles was examined. Thicker films exhibited a red shift in the absorbance maximum for the surface plasmon band which was attributed to the increasing aggregation and cross linking within the film. Quantized double layer charging peaks suggest that film growth is selective toward a specific core size or exchange rate, either of which affect the number of potential linking ligands in the periphery of the MPCs. Multi-layer growth of films was only achieved with metal ions capable of coordinating within the cavity of the 15-crown-5 ether. Our exchange reaction parameters are in stark contrast to other types of MPC film assemblies

Toward Mechanistic Understanding of Nuclear Reprocessing Chemistries by Quantifying Lanthanide Solvent Extraction Kinetics via Microfluidics with Constant Interfacial Area and Rapid Mixing

The closing of the nuclear fuel cycle is an unsolved problem of great importance. Separating radionuclides produced in a nuclear reactor is useful both for the storage of nuclear waste and for recycling of nuclear fuel. These separations can be performed by designing appropriate chelation chemistries and liquid-liquid extraction schemes, such as in the TALSPEAK process (Trivalent Actinide-Lanthanide Separation by Phosphorus reagent Extraction from Aqueous Komplexes). However, there are no approved methods for the industrial scale reprocessing of civilian nuclear fuel in the United States. One bottleneck in the design of next-generation solvent extraction-based nuclear fuel reprocessing schemes is a lack of interfacial mass transfer rate constants obtained under well-controlled conditions for lanthanide and actinide ligand complexes; such rate constants are a prerequisite for mechanistic understanding of the extraction chemistries involved and are of great assistance in the design of new chemistries. In addition, rate constants obtained under conditions of known interfacial area have immediate, practical utility in models required for the scaling-up of laboratory-scale demonstrations to industrial-scale solutions. Existing experimental techniques for determining these rate constants suffer from two key drawbacks: either slow mixing or unknown interfacial area. The volume of waste produced by traditional methods is an additional, practical concern in experiments involving radioactive elements, both from disposal cost and experimenter safety standpoints. In this paper, we test a plug-based microfluidic system that uses flowing plugs (droplets) in microfluidic channels to determine absolute interfacial mass transfer rate constants under conditions of both rapid mixing and controlled interfacial area. We utilize this system to determine, for the first time, the rate constants for interfacial transfer of all lanthanides, minus promethium, plus yttrium, under TALSPEAK process conditions, as a first step toward testing the molecular mechanism of this separation process

Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting'

Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Bacillus cereus and Bacillus anthracis, the anthrax-causing pathogen, directly initiated coagulation of blood in minutes when bacterial cells were clustered. Coagulation of human blood by B. anthracis required secreted zinc metalloprotease InhA1, which activated prothrombin and factor X directly (not via factor XII or tissue factor pathways). We refer to this mechanism as ‘quorum acting’ to distinguish it from quorum sensing—it does not require a change in gene expression, it can be rapid and it can be independent of bacterium-to-bacterium communication

Parylene-C coating protects resin 3D printed devices from materials erosion and prevents cytotoxicity towards primary cells

Resin 3D printing is attractive for rapid fabrication of microscale cell culture devices, but common resin materials are unstable and cytotoxic under culture conditions. Strategies such as leaching or over-curing are insufficient to protect sensitive primary cells such as white blood cells. Here, we evaluated the effectiveness of using parylene-C coating of commercially available clear resins to prevent cytotoxic leaching, degradation of microfluidic devices, and absorption of small molecules. We found that parylene-C significantly improved both the cytocompatibility with primary murine white blood cells and the material integrity of prints, while maintaining the favorable optical qualities held by clear resins

Microfluidics Using Spatially Defined Arrays of Droplets in One, Two, and Three Dimensions

Spatially defined arrays of droplets differ from bulk emulsions in that droplets in arrays can be indexed on the basis of one or more spatial variables to enable identification, monitoring, and addressability of individual droplets. Spatial indexing is critical in experiments with hundreds to millions of unique compartmentalized microscale processes—for example, in applications such as digital measurements of rare events in a large sample, high-throughput time-lapse studies of the contents of individual droplets, and controlled droplet-droplet interactions. This review describes approaches for spatially organizing and manipulating droplets in one-, two-, and three-dimensional structured arrays, including aspiration, laminar flow, droplet traps, the SlipChip, self-assembly, and optical or electrical fields. This review also presents techniques to analyze droplets in arrays and applications of spatially defined arrays, including time-lapse studies of chemical, enzymatic, and cellular processes, as well as further opportunities in chemical, biological, and engineering sciences, including perturbation/response experiments and personal and point-of-care diagnostics

Confinement Regulates Complex Biochemical Networks: Initiation of Blood Clotting by “Diffusion Acting”

This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da2, was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as “diffusion acting”, which is distinct from “diffusion sensing”. The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological “on” and “off” processes that are controlled by thresholds